Monitoring the progress of the acetylation reactions of 4-aminophenol and 2-aminophenol in acetonitrile modified supercritical fluid carbon dioxide and pure acetonitrile using on-line supercritical fluid chromatography and on-line liquid chromatography

• Published in: The Journal of supercritical fluids Vol. 133; pp. 372 - 382
• Main Authors: Li, Ben, Guo, Wei, Ramsey, Edward D.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.03.2018
• Subjects: Acetaminophen SF-CO2 solubility data; Interfaces; Normal phase liquid chromatography; On-line reaction monitoring; Process analytical technology; Supercritical fluid chromatography; Interfaces; Process analytical technology; Acetaminophen SF-CO2 solubility data; Normal phase liquid chromatography; On-line reaction monitoring; Supercritical fluid chromatography
• ISSN: 0896-8446; 1872-8162
• DOI: 10.1016/j.supflu.2017.11.002

[Display omitted] •High pressure SF-CO2 reaction vessel interfaced to on-line SFC or on-line NPLC.•Low pressure reaction equipment interfaced to on-line SFC or on-line NPLC.•Monitoring the progress of acetylation reactions in almost near time.•Accurate solubility data for acetaminophen in SF-CO2.•Reaction yields in SF-CO2 unaffected by any carbamic acid formation. The progress of acetylation reactions of 4-aminophenol and 2-aminophenol in acetonitrile modified SF-CO2 or pure acetonitrile were monitored using on-line SFC or a non-conventional type of on-line normal phase liquid chromatography. For each reaction solvent, acetylations using acetic anhydride were performed at 323K, 333K and 343K. Reactions in SF-CO2 were monitored using a single valve recirculation interface that coupled a high pressure reaction vessel operated at 17.5MPa. Reactions in acetonitrile were monitored using a two valve interface to couple a reaction vessel operated under 0.1MPa nitrogen atmosphere. For both aminophenol isomers, acetylation proceeded more rapidly in acetonitrile modified SF-CO2 compared with acetonitrile. Also for each reaction solvent, the rate of acetylation of 4-aminophenol exceeded that of 2-aminophenol. On-line chromatographic analysis rapidly established that: (i) 4-aminophenol produced a diacetylated product only in acetonitrile modified SF-CO2, whereas (ii) 2-aminophenol produced a diacetylated product only in acetonitrile.